Large-Scale Mapping of Vocalization-Related Activity in the Functionally Diverse Nuclei in Rat Posterior Brainstem

• Published in: The Journal of neuroscience Vol. 42; no. 44; pp. 8252 - 8261
• Main Authors: Concha-Miranda, Miguel, Tang, Wei, Hartmann, Konstantin, Brecht, Michael
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 02.11.2022
• Subjects: Animals; Brain stem; Brain Stem - physiology; c-Fos protein; Circuits; Loudness; Male; Mammals; Mapping; Medulla Oblongata - physiology; Pattern generation; Periaqueductal Gray - physiology; Periaqueductal gray area; Rats; Reticular Formation; Unit activity; Vocalization behavior; Vocalization, Animal - physiology; vocal loudness; brainstem; MdD; NRA; VPG; vocalization
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/JNEUROSCI.0813-22.2022

The identity and location of vocalization pattern generating (VPG) circuits in mammals is debated. Based on physiological experiments, investigators suggested anterior brainstem circuits in the reticular formation, and anatomic evidence suggested the nucleus retroambiguus (NRA) in the posterior brainstem, or combinations of these sites as the putative mammalian VPG. Additionally, vocalization loudness is a critical factor in acoustic communication. However, many of the underlying neuronal mechanisms are still unknown. Here, we evoked calls by stimulation of the periaqueductal gray in anesthetized male rats, performed a large-scale mapping of vocalization-related activity using the activity marker c- , and high-density recordings of brainstem circuits using Neuropixels probes. Both c- expression and recording of vocalization-related activity point to a participation of the NRA in vocalization. More important, among our recorded structures, we found that the NRA is the only brainstem area showing a strong correlation between unit activity and call intensity. In addition, we observed functionally diverse patterns of vocalization-related activity in a set of regions around NRA. Dorsal to NRA, we observed activity specific to the beginning and end of vocalizations in the posterior level of the medullary reticular nucleus, dorsal part, whereas medial and lateral to the NRA, we observed activity related to call initiation. No clear vocalization-related activity was observed at anterior brainstem sites. Our findings suggest a set of functionally heterogeneous regions around the NRA contribute to vocal pattern generation in rats. Vocalization patterns are shaped in the mammalian brainstem, but the identity and location of the circuits involved is debated. Additionally, the neuronal mechanisms of vocal intensity control are still unknown. This study consisted of a large-scale mapping of brainstem vocalization circuits based on the activity marker c- and high-density recordings with Neuropixels probes. The results confirm the role of nucleus retroambiguus in call production and point to a key role of neurons in this nucleus in loudness control. Dorsal to the nucleus retroambiguus and in the posterior medulla, the authors identify neurons with activity specific to the beginning and end of vocalizations. The results point to specific neural dials for various aspects of rat vocalization control in the posterior brainstem.